Immunogenicity and safety of a tetravalent E. coli O-antigen bioconjugate vaccine in animal models.

Autor: van den Dobbelsteen GPJM; Bacterial Vaccines Discovery & Early Development, Janssen Vaccines and Prevention B.V. (former Crucell Holland B.V.), Part of the Janssen Pharmaceutical Companies of Johnson and Johnson, Archimedesweg 4-6, 2333CN Leiden, The Netherlands. Electronic address: gdobbel@its.jnj.com., Faé KC; Bacterial Vaccines Discovery & Early Development, Janssen Vaccines and Prevention B.V. (former Crucell Holland B.V.), Part of the Janssen Pharmaceutical Companies of Johnson and Johnson, Archimedesweg 4-6, 2333CN Leiden, The Netherlands. Electronic address: kfae@its.jnj.com., Serroyen J; Bacterial Vaccines Discovery & Early Development, Janssen Vaccines and Prevention B.V. (former Crucell Holland B.V.), Part of the Janssen Pharmaceutical Companies of Johnson and Johnson, Archimedesweg 4-6, 2333CN Leiden, The Netherlands. Electronic address: jserroy1@its.jnj.com., van den Nieuwenhof IM; Bacterial Vaccines Discovery & Early Development, Janssen Vaccines and Prevention B.V. (former Crucell Holland B.V.), Part of the Janssen Pharmaceutical Companies of Johnson and Johnson, Archimedesweg 4-6, 2333CN Leiden, The Netherlands. Electronic address: Ivanden@its.jnj.com., Braun M; LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Martin.Braun@lmtbio.com., Haeuptle MA; LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland; Current address: Molecular Partners AG, Wagistrasse 14, 8952 Zürich-Schlieren, Switzerland. Electronic address: Micha.Haeuptle@molecularpartners.com., Sirena D; LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Dominique.Sirena@lmtbio.com., Schneider J; LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Joerg.Schneider@lmtbio.com., Alaimo C; LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Cristina.Alaimo@lmtbio.com., Lipowsky G; LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Gerd.Lipowsky@lmtbio.com., Gambillara-Fonck V; LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Veronica.Gambillara@lmtbio.com., Wacker M; LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland; Current address: Wacker Biotech Consulting, Obere Hönggerstrasse 9a, 8103 Unterengstringen, Switzerland. Electronic address: Michael.Wacker@wbioc.com., Poolman JT; Bacterial Vaccines Discovery & Early Development, Janssen Vaccines and Prevention B.V. (former Crucell Holland B.V.), Part of the Janssen Pharmaceutical Companies of Johnson and Johnson, Archimedesweg 4-6, 2333CN Leiden, The Netherlands. Electronic address: JPoolman@its.jnj.com.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2016 Jul 29; Vol. 34 (35), pp. 4152-4160. Date of Electronic Publication: 2016 Jul 06.
DOI: 10.1016/j.vaccine.2016.06.067
Abstrakt: Background: Extra-intestinal pathogenic Escherichia coli (ExPEC) are major human pathogens; however, no protective vaccine is currently available. We assessed in animal models the immunogenicity and safety of a 4-valent E. coli conjugate vaccine (ExPEC-4V, serotypes O1, O2, O6 and O25 conjugated to Exotoxin A from Pseudomonas aeruginosa (EPA)) produced using a novel in vivo bioconjugation method.
Methods: Three doses of ExPEC-4V (with or without aluminum hydroxide) were administered to rabbits (2μg or 20μg per O-antigen, subcutaneously), mice (0.2μg or 2μg per O-antigen, subcutaneously) and rats (0.4μg or 4μg per O-antigen, intramuscularly). Antibody persistence and boostability were evaluated in rats using O6-EPA monovalent conjugate (0.4μg O-antigen/dose, intramuscularly). Toxicity was assessed in rats (16μg total polysaccharide, intramuscularly). Serum IgG and IgM antibodies were measured by ELISA.
Results: Robust antigen-specific IgG responses were observed in all animal models, with increased responses in rabbits when administered with adjuvant. O antigen-specific antibody responses persisted up to 168days post-priming. Booster immunization induced a rapid recall response. Toxicity of ExPEC-4V when administered to rats was considered to be at the no observed adverse effect level.
Conclusions: ExPEC-4V conjugate vaccine showed good immunogenicity and tolerability in animal models supporting progression to clinical evaluation.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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